The undecapeptide substance P(SP) was shown to be intimately involved in both the structural and functional aspects of the anterior pituitary. Yet, in addition to its influences on hormonal secretion, SP may well poss...The undecapeptide substance P(SP) was shown to be intimately involved in both the structural and functional aspects of the anterior pituitary. Yet, in addition to its influences on hormonal secretion, SP may well possess more actions in this master gland. The present study was ftherefore aimed to investigate the effect of SP on the proliferation of rat anterior pituitary cells in primary culture. It was found that SP could dose-dependently increase the ineorporation of tritiated thymidine (3H-TdR)into cultured anterior pituitary cells. Other mammalian tachykinins such as neurokinin A and neurokinin B had similar effect but to varying degrees. The equipotent analogue of SP, Norleucine(11) -SP(Nle(11)-SP), also acted likewise, with its action antagonizable by spantide, a SP receptor blocker. To further characterize the nature of cells responsive to the challenge of SP, immunocytochemical staining against S-100 protein and some adenohypophyseal hormones was performed alone or plus autoradiography The results showed that the percentage of S-100 proteinimmunoreactive cells was apparently elevated by the addtion of Nle(11)-SP for 48 h, which indicates a preferential proliferation of folliculo-stellate cells under the regime. This was confirmed by increases in immunocytochemical or autoradiographical labelling indices of anterior pituitary cells treated similarly. Taken togethbr, these results reveal that the trophic action of SP observed previously in other tissues is also present at least in cultured rat anterior pituitary cells, with responding cells being predominantly folliculo-stellate cells as typified by S-100 proteinimmunoreactivity. Therefore, an intra-pituitary trophic action of SP in vivo could be anticipated.展开更多
We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in...We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in the acupuncture effect; Υ-aminobutyric-acid system perhaps participated in this effect.This paper further provided evidence that central serotonin and EOP play a stimulatory role in the acupuncture induced secretion of prolactin; acupuncture may antagonize inhibitory effect of H<sub>2</sub> histamine receptor activation on prolactin secretion; the possible role of H<sub>1</sub>-receptor needs further investigation.展开更多
On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental pertur...On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.展开更多
Long COVID has been studied as different sequelae that some individuals can develop after the acute phase of the disease. Persistent symptoms such as dry cough, fatigue, and dyspnea can remain after six months of COVI...Long COVID has been studied as different sequelae that some individuals can develop after the acute phase of the disease. Persistent symptoms such as dry cough, fatigue, and dyspnea can remain after six months of COVID-19 cure. Others such as lung fibrosis, kidney injury, and thrombotic risk also are observed. Here, a deep review of each human organ and system infected by the virus was performed aiming to show how molecules expression and cell signaling can induce the organism cure or injuries and, subsequently sequelae. The review also suggests the importance of public health surveillance for these cases including a more comprehensive analysis of molecular biology tools that can clarify and assist in the prognosis, treatment, and preventive methods for potentially more serious disorders in post-COVID-19 patients.展开更多
Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor i...Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.展开更多
Adrenomedullin,a peptide with multiple physiological functions in nervous system injury and disease,has aroused the interest of researchers.This review summarizes the role of adrenomedullin in neuropathological disord...Adrenomedullin,a peptide with multiple physiological functions in nervous system injury and disease,has aroused the interest of researchers.This review summarizes the role of adrenomedullin in neuropathological disorders,including pathological pain,brain injury and nerve regeneration,and their treatment.As a newly characterized pronociceptive mediator,adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain,cancer pain,neuropathic pain induced by spinal nerve injury and diabetic neuropathy.Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance.Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury.Additionally,adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions.Therefore,adrenomedullin is an important participant in nervous system diseases.展开更多
The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficienc...The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.展开更多
While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression...While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract(AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine(SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.展开更多
To analyze the kinetics and size of single exo- and endocytotic events in BY-2 protoplasts, we employed cellattached membrane capacitance measurements. These measurements revealed different modes of fusion and fission...To analyze the kinetics and size of single exo- and endocytotic events in BY-2 protoplasts, we employed cellattached membrane capacitance measurements. These measurements revealed different modes of fusion and fission of single vesicles. In about half of the observed exocytotic events, fusion occurred transiently, which facilitates rapid recycling of vesicles. In addition, transient sequential or multi-vesicular exocytosis observed in some recordings can contribute to an increase in efficiency of secretory product release. Microscopic analysis of the timescale of cellulose and pectin deposition in protoplasts demonstrates that rebuilding of the cell wall starts soon after isolation of protoplasts and that transient fusion events can fully account for secretion of the required soluble material. The capacitance measurements also allowed us to investigate formation of the fusion pore. We speculate that regulation of secretion may involve control of the length and/or size of fusion pore opening. Together, the different kinetic modes of exo- and endocytosis revealed by capacitance measurements underline the complexity of this process in plants and provide a basis for future research into the underlying mechanisms. The fact that similar fusion/fission kinetics are present in plant and animal cells suggests that many of these mechanisms are highly conserved among eukaryotes.展开更多
Esomeprazole,one of the proton pump inhibitors(PPIs),has been widely used in acid-related diseases,such as gastro-esophageal reflux disease and Helicobacter pylori infection.Compared with other PPIs,esomeprazole has h...Esomeprazole,one of the proton pump inhibitors(PPIs),has been widely used in acid-related diseases,such as gastro-esophageal reflux disease and Helicobacter pylori infection.Compared with other PPIs,esomeprazole has higher acid control efficiency,bioavailability,stability,and less interindividual variation depending on its pharmacokinetic properties.Esomeprazole was considered safe for long-term administration.However,several recent studies have contradicted its absolute safety,and some detrimental cases have been reported in some special groups,such as pregnant women and patients with liver cirrhosis.Because acid-related diseases usually require long-term therapy and esomeprazole inhibits CYP2C19 enzyme that increases the probability of drug-drug interaction,these risks have become a concern.Recent studies have shown that esomeprazole not only inhibits acid secretion,but also exhibits acid-independent effects in inflammatory conditions.Esomeprazole can modulate NF-κb activation to resist tissue oxidation and apoptosis in gastric ulcer.In CCL4-induced liver fibrosis,esomeprazole improves oxidative stress,fibrogenesis,and apoptosis,but the mechanism still remains unclear.This review summarized the property of esomeprazole and its potential risk for administration,and its latest research progress,which may facilitate clinicians to better use and avoid the potential risks.展开更多
Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsych...Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome.Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions.Astroglia respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and function.In addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS pathologies.Astroglial pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and sex.Here,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive disease.We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric disorders.Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.展开更多
文摘The undecapeptide substance P(SP) was shown to be intimately involved in both the structural and functional aspects of the anterior pituitary. Yet, in addition to its influences on hormonal secretion, SP may well possess more actions in this master gland. The present study was ftherefore aimed to investigate the effect of SP on the proliferation of rat anterior pituitary cells in primary culture. It was found that SP could dose-dependently increase the ineorporation of tritiated thymidine (3H-TdR)into cultured anterior pituitary cells. Other mammalian tachykinins such as neurokinin A and neurokinin B had similar effect but to varying degrees. The equipotent analogue of SP, Norleucine(11) -SP(Nle(11)-SP), also acted likewise, with its action antagonizable by spantide, a SP receptor blocker. To further characterize the nature of cells responsive to the challenge of SP, immunocytochemical staining against S-100 protein and some adenohypophyseal hormones was performed alone or plus autoradiography The results showed that the percentage of S-100 proteinimmunoreactive cells was apparently elevated by the addtion of Nle(11)-SP for 48 h, which indicates a preferential proliferation of folliculo-stellate cells under the regime. This was confirmed by increases in immunocytochemical or autoradiographical labelling indices of anterior pituitary cells treated similarly. Taken togethbr, these results reveal that the trophic action of SP observed previously in other tissues is also present at least in cultured rat anterior pituitary cells, with responding cells being predominantly folliculo-stellate cells as typified by S-100 proteinimmunoreactivity. Therefore, an intra-pituitary trophic action of SP in vivo could be anticipated.
基金Project supported by the National Natural Science Fund
文摘We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in the acupuncture effect; Υ-aminobutyric-acid system perhaps participated in this effect.This paper further provided evidence that central serotonin and EOP play a stimulatory role in the acupuncture induced secretion of prolactin; acupuncture may antagonize inhibitory effect of H<sub>2</sub> histamine receptor activation on prolactin secretion; the possible role of H<sub>1</sub>-receptor needs further investigation.
文摘On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.
文摘Long COVID has been studied as different sequelae that some individuals can develop after the acute phase of the disease. Persistent symptoms such as dry cough, fatigue, and dyspnea can remain after six months of COVID-19 cure. Others such as lung fibrosis, kidney injury, and thrombotic risk also are observed. Here, a deep review of each human organ and system infected by the virus was performed aiming to show how molecules expression and cell signaling can induce the organism cure or injuries and, subsequently sequelae. The review also suggests the importance of public health surveillance for these cases including a more comprehensive analysis of molecular biology tools that can clarify and assist in the prognosis, treatment, and preventive methods for potentially more serious disorders in post-COVID-19 patients.
文摘Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.
基金supported by the National Natural Science Foundation of China,No.81400922(to DMW),81571084the Natural Science Foundation of Fujian Province of China,No.2018J01813(to DMW)the College of Life Sciences of Fujian Normal University of China,No.FZSKG2018016(to DMW)
文摘Adrenomedullin,a peptide with multiple physiological functions in nervous system injury and disease,has aroused the interest of researchers.This review summarizes the role of adrenomedullin in neuropathological disorders,including pathological pain,brain injury and nerve regeneration,and their treatment.As a newly characterized pronociceptive mediator,adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain,cancer pain,neuropathic pain induced by spinal nerve injury and diabetic neuropathy.Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance.Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury.Additionally,adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions.Therefore,adrenomedullin is an important participant in nervous system diseases.
基金funded by the Russian Science Foundation(RSF)(research project N°16-15-10053(extension)).
文摘The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.
文摘While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract(AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine(SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
文摘To analyze the kinetics and size of single exo- and endocytotic events in BY-2 protoplasts, we employed cellattached membrane capacitance measurements. These measurements revealed different modes of fusion and fission of single vesicles. In about half of the observed exocytotic events, fusion occurred transiently, which facilitates rapid recycling of vesicles. In addition, transient sequential or multi-vesicular exocytosis observed in some recordings can contribute to an increase in efficiency of secretory product release. Microscopic analysis of the timescale of cellulose and pectin deposition in protoplasts demonstrates that rebuilding of the cell wall starts soon after isolation of protoplasts and that transient fusion events can fully account for secretion of the required soluble material. The capacitance measurements also allowed us to investigate formation of the fusion pore. We speculate that regulation of secretion may involve control of the length and/or size of fusion pore opening. Together, the different kinetic modes of exo- and endocytosis revealed by capacitance measurements underline the complexity of this process in plants and provide a basis for future research into the underlying mechanisms. The fact that similar fusion/fission kinetics are present in plant and animal cells suggests that many of these mechanisms are highly conserved among eukaryotes.
基金National Natural Science Foundation of Chinagrant number 81900535
文摘Esomeprazole,one of the proton pump inhibitors(PPIs),has been widely used in acid-related diseases,such as gastro-esophageal reflux disease and Helicobacter pylori infection.Compared with other PPIs,esomeprazole has higher acid control efficiency,bioavailability,stability,and less interindividual variation depending on its pharmacokinetic properties.Esomeprazole was considered safe for long-term administration.However,several recent studies have contradicted its absolute safety,and some detrimental cases have been reported in some special groups,such as pregnant women and patients with liver cirrhosis.Because acid-related diseases usually require long-term therapy and esomeprazole inhibits CYP2C19 enzyme that increases the probability of drug-drug interaction,these risks have become a concern.Recent studies have shown that esomeprazole not only inhibits acid secretion,but also exhibits acid-independent effects in inflammatory conditions.Esomeprazole can modulate NF-κb activation to resist tissue oxidation and apoptosis in gastric ulcer.In CCL4-induced liver fibrosis,esomeprazole improves oxidative stress,fibrogenesis,and apoptosis,but the mechanism still remains unclear.This review summarized the property of esomeprazole and its potential risk for administration,and its latest research progress,which may facilitate clinicians to better use and avoid the potential risks.
基金grants from NSFC-RSF(82261138557)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202003)+3 种基金the Sichuan Science and Technology Program(2022YFH0006)Y.T.was supported by NSFC(82274668,82230127)Sichuan Provincial Administration of Traditional Chinese Medicine(2023zd024).Work in the M.V.S.laboratory is supported by National Institutes of Health(NS084030)by the Dr.Miriam and Sheldon G.Adelson Medical Foundation.
文摘Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome.Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions.Astroglia respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and function.In addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS pathologies.Astroglial pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and sex.Here,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive disease.We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric disorders.Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.